Background
Methods
Study design and oversight
Patients and procedures
Randomization and interventions
Study measurements
Study endpoints
Statistical analysis
Results
Participants’ baseline characteristics
Characteristics | CPAP group N = 153 | Usual-care group N = 157 | p value |
---|---|---|---|
Age (year), mean (SD) | 32.9 ± 5.3 | 32.6 ± 5.1 | 0.553 |
Gestational age at enrollment (week), mean (SD) | 11.18 ± 4.0 | 10.26 ± 3.14 | 0.908 |
Gestational age at randomization (week), mean (SD) | 15.2 ± 4.8 | 14.5 ± 4.5 | 0.180 |
Nulliparous, no. (%) | 49 (32.0) | 56 (35.7) | 0.498 |
Anthropometric measurement | |||
Pre-pregnancy body mass index (kg/m2)a, mean (SD) | 29.2 ± 5.8 | 29.6 ± 5.5 | 0.546 |
Body mass index at enrollment (kg/m2), mean (SD) | 30.1 ± 5.9 | 30.4 ± 5.5 | 0.722 |
Neck circumference (cm), mean (SD) | 35.4 ± 3.3 | 35.4 ± 3.2 | 0.977 |
Waist circumference (cm), mean (SD) | 97.7 ± 12.6 | 97.7 ± 11.0 | 0.971 |
Type of inclusion criteriab, no. (%) | |||
Obesityc | 99 (64.7) | 111 (70.7) | 0.259 |
Chronic hypertension | 27 (17.7) | 23 (14.7) | 0.473 |
Pre-existing hypertension before pregnancy | 25 (16.3) | 21 (13.4) | 0.463 |
Hypertension occurring before 20 weeks of gestation | 10 (6.5) | 8 (5.1) | 0.588 |
History of preeclampsia in previous pregnancy | 13 (8.5) | 14 (8.9) | 0.896 |
History of gestational hypertension in previous pregnancy | 3 (2.0) | 4 (2.5) | 0.728 |
Known case of diabetes mellitus | 12 (7.8) | 13 (8.3) | 0.888 |
History of gestational diabetes in previous pregnancy | 29 (19.0) | 28 (17.8) | 0.799 |
Gestational diabetes detected early | 72 (47.1) | 70 (44.6) | 0.662 |
Epworth Sleepiness Scaled, median (IQR) | 8.5 (5.0, 11.0) | 8.0 (5.0, 12.0) | 0.093 |
Epworth Sleepiness Scale ≥ 11, no., % | 48 (31.4) | 51 (32.5) | 0.833 |
Report of frequent snoring ≥ 3 times/weeke, no. (%) | 76 (49.7) | 78 (49.7) | 0.999 |
Systolic blood pressure (mmHg), mean (SD) | 116.9 ± 1.3 | 116.0 ± 1.1 | 0.574 |
Diastolic blood pressure (mmHg), mean (SD) | 73.5 ± 0.9 | 73.9 ± 0.7 | 0.706 |
Mean blood pressure (mmHg), mean (SD) | 88.1 ± 0.8 | 88.1 ± 1.0 | 0.989 |
Fasting plasma glucose (mg/dL), mean (SD) | 99.3 ± 28.1 | 101.4 ± 35.8 | 0.581 |
Hemoglobin A1C (mg/dL), mean (SD) | 5.4 ± 0.8 | 5.6 ± 1.0 | 0.211 |
Polysomnographic parameter | CPAP group N = 153 | Usual-care group N = 157 | p value |
---|---|---|---|
Total sleep time (hour), mean (SD) | 6.0 ± 1.0 | 6.2 ± 0.8 | 0.044 |
Sleep efficiency (%), mean (SD) | 84.7 ± 11.6 | 85.9 ± 8.8 | 0.329 |
Sleep latency (minute), median (IQR) | 14.4 (7.8, 25.7) | 13.6 (7.5, 27.8) | 0.730 |
Stage N1 and N2 (%), mean (SD) | 62.6 ± 8.3 | 63.4 ± 8.3 | 0.371 |
Stage N3 (%), mean (SD) | 20.6 ± 7.7 | 19.2 ± 7.3 | 0.085 |
Stage REM (%), mean (SD) | 16.8 ± 5.0 | 17.4 ± 5.2 | 0.276 |
Sleep time during supine position (%), mean (SD) | 69.1 ± 24.8 | 65.6 ± 24.2 | 0.080 |
Respiratory disturbance index (RDI)a (events/hour), mean (SD) | 14.1 ± 6.6 | 14.9 ± 6.6 | 0.948 |
Apnea–hypopnea index (AHI)b (events/hour), median (IQR)b | 7.0 (4.4, 12.5) | 7.2 (4.4, 13.5) | 0.813 |
Apnea index (events/hour), median (IQR) | 0.2 (0.0, 1.2) | 0.3 (0.0, 0.9) | 0.262 |
Hypopnea index (events/hour), median (IQR) | 6.4 (4.2, 10.1) | 6.9 (4.0, 11.8) | 0.453 |
Apnea–hypopnea index in REM sleep (events/hour), median (IQR) | 16.1 (7.6, 31.3) | 14.1 (7.6, 24.0) | 0.249 |
Apnea–hypopnea index in NREM sleep (events/hour), median (IQR) | 5.1 (2.6, 11.4) | 6.8 (2.8, 11.8) | 0.041 |
Apnea–hypopnea index during supine position (events/hour), median (IQR) | 13.9 (9.5, 20.9) | 15.6 (8.7, 21.2) | 0.176 |
Apnea–hypopnea index during non-supine position (events/hour), median (IQR) | 5.1 (2.6, 8.5) | 5.1 (2.0, 10.2) | 1.000 |
Oxygen desaturation indexc (events/hour), median (IQR) | 1.9 (0.6, 4.3) | 2.6 (0.9, 5.2) | 0.372 |
Average oxygen saturation (%), mean (SD) | 96.7 ± 1.1 | 96.6 ± 1.0 | 0.455 |
Minimum oxygen saturation (%), mean (SD) | 89.4 ± 4.2 | 89.2 ± 3.9 | 0.686 |
Time oxygen saturation under 90% (minutes), median (IQR) | 0 (0, 0.06) | 0 (0, 0.07) | 0.359 |
Obstructive sleep apnea characteristics | |||
Severityd, no. (%) | |||
Mild | 71(46.4) | 73(46.5) | 0.987 |
Moderate | 82(53.6) | 84(53.5) | |
In-laboratory polysomnography, no. (%) | 152 (99.4) | 156 (99.4) | 1.0 |
Agreement between scorers (%), mean (SD) | 89.0 ± 10.2 | 90.0 ± 11.8 | 0.433 |
Medication use, no. (%) | CPAP group N = 153 | Usual-care group N = 157 | p value |
---|---|---|---|
Antihypertensive agent use, no. (%) | 12 (7.8) | 12 (7.6) | 0.947 |
Methyldopa, no. (%) | 11 (7.2) | 12 (7.6) | 0.307 |
Initial dose (mg/day), median (IQR) | 500 (250, 750) | 500 (500, 750) | 0.129 |
Final dose (mg/day), median (IQR) | 750 (500, 750) | 500 (250, 750) | 0.339 |
Hydralazine, no. (%) | 3 (25.0) | 8 (66.7) | 0.041 |
Initial dose (mg/day), median (IQR) | 62.5 (37.5, 87.5) | 50.0 (37.5, 75) | 0.441 |
Final dose (mg/day), median (IQR) | 75 (37.5, 200) | 75 (50, 75) | 0.267 |
Combined methyldopa and hydralazine, no. (%) | 2 (16.7) | 8 (66.7) | 0.013 |
Additional 3rd anti-hypertensive medication, no. (%) | 1 (8.3) | 3 (25.0) | 0.273 |
MgSO4 stabilization during delivery, no. (%) | 4 (33.3) | 10 (83.3) | 0.013 |
Insulin—no. (%) | 33 (21.6) | 32 (20.4) | 0.798 |
Insulin dose (u/day), median (IQR) | 32 (3, 160) | 46 (6, 140) | 0.217 |
Other medications | |||
Aspirin, no. (%) | 35 (22.9) | 40 (25.5) | 0.593 |
Calcium supplement, no. (%) | 53 (34.6) | 50 (31.9) | 0.602 |
Vitamin D supplement, no. (%) | 6 (4.8) | 2 (1.7) | 0.142 |
Adherence to intervention
Effect of CPAP on BPs
Modified intention-to-treat analysis | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean (SE)a | CPAP (n = 153) | Usual-care (n = 157) | Overall mean | Intergroup difference (95%CI)c | p value | Adjusted intergroup difference (95%CI)d | p value | |||||
18–20 weeksb | 24–28 weeks | 32–34 weeks | 18–20 weeksb | 24–28 weeks | 32–34 weeks | CPAP vs control | ||||||
SBP | 114.7 (1.0) | 112.5 (1.0) | 115.2 (1.0) | 116.7 (1.0) | 114.4 (1.0) | 117.2 (1.0) | 114.1 (1.0) | 116.1 (0.9) | − 1.9 (− 4.5, 0.6) | 0.148 | − 2.08 (− 4.41, 0.26) | 0.082 |
DBP | 70.4 (0.7) | 69.3 (0.7) | 71.3 (0.7) | 72.6 (0.7) | 71.5 (0.7) | 73.8 (0.7) | 70.4 (0.6) | 72.5 (0.6) | − 2.2 (− 3.9, − 0.4) | 0.014 | − 2.22 (− 3.70, − 0.75) | 0.003 |
MAP | 85.2 (0.8) | 83.7 (0.8) | 86.0 (0.8) | 87.3 (0.7) | 85.8 (0.7) | 88.0 (0.7) | 85.0 (0.7) | 87.0 (0.7) | − 2.1 (− 3.9, − 0.2) | 0.034 | − 2.17 (− 3.83, − 0.52) | 0.010 |
Effect of CPAP on pregnancy outcomes
Endpoints | CPAP group | Usual-care group | Risk difference, % (95%CI)a | Number needed to treat (95%CI)a | p value |
---|---|---|---|---|---|
Modified intention to treat analysis | (n = 153) | (n = 157) | |||
Preeclampsia, no. (%) | 20 (13.1) | 35 (22.3) | − 9 (− 18, − 1) | 11 (1, 21) | 0.032 |
Severe preeclampsiab | 13 (8.5) | 22 (14.0) | − 6 (− 14, 13) | – | 0.122 |
Early-onset preeclampsiac | 4 (2.6) | 4 (2.6) | 0.1 (− 4, 3.5) | – | 0.97 |
Late-onset preeclampsiad | 16 (10.5) | 31 (19.8) | − 9 (− 17, − 1.4) | 11 (2, 20) | 0.021 |
Hypertensive disorders in pregnancye, no. (%) | 21 (13.7) | 39 (24.8) | − 11 (− 20, − 2) | 9 (2, 16) | 0.012 |
Post-hoc analyses
Per-protocol and counterfactual analyses
Usual-care (n = 157) | CPAP non-adherent subgroup (n = 103) | CPAP-adherent subgroup (n = 50) | p value | |
---|---|---|---|---|
Treatment effect | ||||
Overall mean blood pressure (SE) after randomization | ||||
Systolic blood pressure, mmHg | 116.07 (0.92) | 115.11 (1.16) | 112.22 (1.64) | |
∆Overall differencea | Reference | − 0.96 (− 3.87, 1.95) | − 3.85* (− 7.54, − 0.14) | 0.041 |
∆Adjusted overall differenceb | Reference | − 0.83 (− 3.43, 1.77) | − 4.38* (− 7.68, − 1.08) | 0.009 |
Diastolic blood pressure, mmHg | 72.50 (0.61) | 70.89 (0.77) | 69.28 (1.08) | |
∆Overall differencea | Reference | − 1.61 (− 3.53, 0.305) | − 3.23* (− 5.66, − 0.79) | 0.009 |
∆Adjusted overall differenceb | Reference | − 1.48 (− 3.11, 0.16) | − 3.54* (− 5.62, − 1.46) | 0.009 |
Mean arterial blood pressure, mmHg | 87.03 (0.68) | 85.64 (0.86) | 83.59 (1.21) | |
∆Overall differencea | Reference | − 1.39 (− 3.54, 0.75) | − 3.44* (− 6.16, − 0.71) | 0.013 |
∆Adjusted overall differenceb | Reference | − 1.26 (− 3.10, 0.59) | − 3.83* (− 6.17, − 1.49) | 0.001 |
Endpoints | CPAP group | Usual-care group | Risk difference, % (95%CI)a | Number needed to treat (95%CI)a | p value |
---|---|---|---|---|---|
Per-protocol analysis | (n = 50) | (n = 155) | |||
Preeclampsia, no. (%) | 6 (12.0) | 35 (22.6) | − 11 (− 22, 6) | – | 0.124 |
Severe preeclampsiab | 6 (12.0) | 22 (14.19) | − 2 (− 8, 13) | – | 0.684 |
Early preeclampsiac | 4 (8.0) | 4 (2.58) | 5 (− 13, 3) | – | 0.180 |
Late preeclampsiad | 2 (4.0) | 31 (20.0) | − 16 (− 24, − 8) | 7 (3, 10) | 0.024 |
Hypertensive disorders in pregnancye, no. (%) | 7(14.0) | 39(25.2) | − 11 (− 23, 1) | – | 0.120 |
Counterfactual analysis | (n = 52) | (n = 258) | |||
Preeclampsia, no. (%) | 6 (11.5) | 49 (19.0) | − 17 (− 27, − 6) | 6 (2, 10) | < 0.001 |
Severe preeclampsiab | 6 (11.54) | 29 (11.24) | 9 (− 19, 0.4) | – | 0.062 |
Early preeclampsiac | 4 (7.69) | 4 (1.55) | 2 (− 5, 5) | – | 0.938 |
Late preeclampsiad | 2 (3.85) | 45 (17.44) | − 18 (− 27, − 10) | 6 (3, 8) | < 0.001 |
Hypertensive disorders in pregnancye, no. (%)e | 7 (13.5) | 53 (20.5) | − 19 (− 30, − 9) | 5 (2, 8) | < 0.001 |